The present invention relates to new improved formulations for application to a mucosal tissue, and to methods of preparation of these formulations. These formulations are useful for oral administration, such as mouth wash or oral rinse formulations. More specifically, the present invention concerns improved formulations including a lipid carrier and biologically active agent dispersed in a continuous aqueous phase. The lipid carrier is characterized by having high adhesive capabilities towards mucous membranes such as those of the gums, tongue and palate. The lipid carrier also has a high load capacity for the biologically active agent. As such, the lipid carrier can specifically target a relatively large amount of the agent to these mucous membranes to ensure a controlled and sustained release of the agent at the mucous surface.
In the field of personal care and hygiene, many different formulations have been designed and employed commercially in a wide variety of “over-the-counter” medications and products for a number of purposes including oral hygiene and skin care. Many of these medications and products contain both a biologically active agent such, as for example, an anti-microbial agent, and an inert vehicle. The particular choice of vehicle depends upon the desired properties of the formulation.
However, the currently available formulations for personal care and hygiene products suffer from a number of drawbacks, including lack of suitability of the carrier for its intended use. Most of these known formulations suffer from an inability to carry a large amount of the active agent and to ensure a controlled and prolonged release thereof at the desired site. This inability is particularly undesirable, since usually any biologically active agent must remain at the desired site for a prolonged period in order to be effective.
Recently, liposome-based delivery systems have been developed in which the active agent is encapsulated within a multilamellar lipid vesicle or liposome, and is then released in a controlled fashion from the liposome. For example, U.S. Pat. No. 4,588,578 discloses lipid vesicles in which the active ingredient is encapsulated, rather than being complexed with a lipid. However, such liposomes suffer from the drawback of having a limited load capacity for the active agent.
Furthermore, many of these liposomes and related lipid particles are not suitable for long term storage, particularly at ambient temperatures. An example of a liposome-based delivery system has been disclosed in U.S. Pat. No. 4,767,615, in which specific modifications to the lipid structure enable specific targeting of the liposome to specific tissues, such as the enamel of the teeth. Conversely, the very specificity of such carriers limits them to tissues covered by an enamel layer. Furthermore, the maximum capacity for the active agent is only about 20% of the liposome volume of the disclosed prior art carrier.
As another example, U.S. Pat. No. 5,415,867 discloses lipid particles with a relatively high ratio of agent to lipid. However, this reference does not teach or disclose the use of such particles for administration to a mucosal tissue or mucous membrane. Instead, the reference primarily teaches parenteral administration. Similarly, PCT Application No. WO 92/03121 discloses only colloidal particles for oral administration or for administration on the intact skin. Thus, the prior art does not teach the use of high ratio lipid particles for administration to a mucous membrane or mucosal surface.
Furthermore, the known non-liposome, hydrophilic, water soluble formulations also suffer from a very short retention time at the tissue to which they are applied, because they are readily washed away or degraded.
In view of the above drawbacks of the prior art carriers, there has been a long-felt need to provide formulations for personal care and hygiene which are multi-purpose and can be applied to a mucosal tissues. Such carriers must have high adhesion capability to ensure contact for a prolonged time, and must be able to carry a high amount of active agent to the site of adhesion for a controlled and prolonged release to the desired tissue.
Other aims and aspects of the present invention will be apparent from the following description of the present invention.